In vivo CHRONIC PELVIC PAIN INDUCED BY CARRAGEENAN A MODEL FOR CHRONIC PROSTATITIS / CHRONIC PELVIC PAIN SYNDROME (CP/CPPS) MODEL Intraprostatic injection of carrageenan induces pelvic pain Effects on the nociceptive threshold (A), the nociceptive scores (B) and the AUC (C), 3 days post-injection. A Nociceptive threshold (g) Inflammatory chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS), also referred as NIH category IIIA prostatitis, is characterised by an abacterial inflammation of the prostate, associated with pelvic pain. It is the most common type of prostatitis in human. Inflammatory CP/CPPS is induced by intraprostatic injection of carrageenan; a seaweed polysaccharide which is widely used to induce inflammatory pain in animal models. SPECIE Rat ns ns 1.5 1.0 ns= p>0.05, ** p<0.01, Kruskal-Wallis test. (n=6-16) Values represent mean ± s.e.m. 0.5 0.0 Naive MODEL DESCRIPTION • The pelvic sensitivity to mechanical stimuli is assessed using von Frey filaments of different forces that are applied to the scrotum area. • Mechanical stimulations are performed, in conscious animals, at different time points after carrageenan injection (from 1d to 7d). • Tested compounds can be administered via various routes (i.v., i.p., s.c., p.o.). Nociceptive scores (%) B 60 Naive 50 Carrageenan 30 *** 20 10 0 0.0 0.5 1.0 1.5 ns= p>0.05, *** p<0.001, Two-way ANOVA with repeated mesures.(n=6-16) Values represent mean ± s.e.m. 2.0 C ns ns 80 *** *** 70 60 50 40 ns= p>0.05, *** p<0.001, One-way ANOVA. (n=6-16) Values represent mean ± s.e.m. 30 20 10 0 Naive Saline Carrageenan Intraprostatic injection Ibuprofen (300 mg/kg, p.o.) and morphine (3 mg/kg, s.c.) reverse carrageenan-induced pelvic pain. PARAMETERS EVALUATED 80 • Nociceptive threshold • Area under the curve (AUC) by plotting nociceptive scores against von Frey force SCIENTIFIC PUBLICATIONS Chen CS et al., Prostate 73: 391-7, 2013 Mosli HA et al., BJUI int. 110: 274-82, 2012 Chen RZ et al., J. Ethnopharmacol. 134: 1018-23, 2011 Radhakrishnan R, Inflammopharmacol. 17: 23-28, 2009 UROsphere is a pre-clinical company specializing in in vitro and in vivo pharmacological studies for Urogenital and Renal disorders - http://www.urosphere.com *** *** 70 AUC (0.16-2 g) • Nociceptive scores (%) • • • • ns Saline 40 von Frey forces (g) AUC (0.16-2 g) • This model of inflammation-induced pelvic pain is a rapid and relevant preclinical model to test therapeutic approaches for the treatment of inflammatory CP/CPPS. Saline Carrageenan Intraprostatic injection INTEREST • This model is characterized by allodynia (decreased threshold in response to innocuous von Frey forces) and hyperalgesia (increased nociceptive scores in response to noxious von Frey forces). • Compounds that reverse carrageenan effects in this model include: a non-steroidal anti-inflammatory drugs (ibuprofen) and an opioid receptor agonist (morphine). ** ** 60 50 40 30 20 10 0 Vehicle Ibuprofen Vehicle Morphine Carrageenan Intraprostatic injection *** p<0.001, Unpaired t test. (n=4-7) Values represent mean ± s.e.m. © UROsphere 2014. All rights reserved. Non contractual document